Transdermal drug delivery is an increasingly important method of drug administration. Transdermal drug delivery patches are similar in appearance to adhesive bandages, and--when attached onto the skin--deliver pharmaceutically and cosmetically active substances (hereinafter referred to abbreviated as "active substances" and interchangeably used with the term "bioactive substances" and "drug(s)") through the skin. Transdermal drug delivery patches dispense a drug at a controlled rate by presenting the drug for absorption in a efficient manner with a minimum of degradation of the drug, and prevent complications from failure of a patient to comply with a therapeutic regimen. In cosmetic applications, where the desired objective is to deliver effective concentrations of the bioactive substance, such as ascorbic acid, directly to the underlying tissue (the dermal layer) of the skin, transdermal patches have been found to be ideal delivery devices.
Of increasing interest are adhesive matrix type transdermal drug delivery patches in which the bioactive substance is incorporated into a pressure sensitive adhesive layer, which serves not only to carry the bioactive substance but to also attach the patch to the skin. The adhesive matrix type transdermal patch is of simple construction, and is typically comprised of an impermeable backing layer, a single pressure sensitive adhesive, i.e., self-adhesive, layer, the matrix, and a removable protective layer that comprises a release liner. Since the function of such transdermal or dermal (i.e., only topically effective), therapeutic or cosmetic patches and the materials required for their production are well known in the prior art, it will suffice to only mention that one or more bioactive substances are mixed in the pressure sensitive matrix, and that after application of the patch onto the intact skin, the active substances diffuse from the patch into the skin, developing a local or systemic effect.
The adhesive matrix layers are typically manufactured in such a manner that components of the adhesive and their solvents, are mixed with bioactive substances and then coated on a suitable sheet, intended to function as a disposable liner, and the solvents are removed in a drying process. Next, a non-releaseable backing layer is applied over the adhesive matrix layer. The result is a web comprised of a pressure sensitive adhesive matrix layer, containing the bioactive substance(s), sandwiched between a backing layer on one side and a disposable release liner on the other. The web is die cut into suitable sizes and shapes to produce pressure sensitive adhesive transdermal drug delivery patches.
The manufacturing process has serious disadvantages, namely: it is a costly batch-type method which requires a proper mixing of the various ingredients and it is time constrained once the ingredients are mixed together, resulting in a fixed size production runs. Additionally, bioactive substances, as well as the various adjuvants used, may interact adversely with components of the adhesive in the formation reaction of the adhesive. A need therefore exists for methods for making pressure sensitive adhesive matrix type transdermal patches in a economical and continuous process, whereby the bioactive substances do not participate in the formation of the pressure sensitive adhesive matrix layer; and whereby a high concentration of bioactive substances in powder form produces a usable product.
Prior art examples of patches for transdermal delivery of cosmetically active substances include:
U.S. Pat. No. 2,001,862 (Battey; May 1935) discloses adhesive patches in a crescent form or other shapes, medicated with alum for the treatment of wrinkles. The adhesive is dried dextrin, which becomes tacky when wetted with water. PA1 U.S. Pat. No. 3,896,789 (Trancik; July 1975), discloses a pressure sensitive adhesive tape, whose adhesive layer contains a retinoic acid and vitamin E, used for topical treatment of skin diseases. PA1 U.S. Pat. No. 3,949,741 (Hofmann; April 1976), discloses a wrinkle-reducing method whereby pressure sensitive adhesive patches of appropriate shapes are applied to wrinkle-prone areas of the human skin. The adhesive layer of the patch may contain "a small amount of mild acids which promote sloughing off of dead cells on the outer layer of the skin". PA1 U.S. Pat. No. 5,100,672 (Gueret, et al; March 1992) discloses a pressure sensitive adhesive transdermal patch having a composite adhesive layer reinforced with a web layer. Cosmetically bioactive substances used in the patch include water soluble vitamins such as vitamin C, and liposoluble vitamins A and E or their derivatives. PA1 GB 2,265,086 A (Hanet, et al) patent application published on Sep. 22, 1993, discloses the formulation of ascorbic acid and its derivatives, including Sodium Absorbate, into skin whitening pressure sensitive adhesive transdermal patches. PA1 WO 96/14822 patent application (Porter, et al), published on May 23, 1996, discloses a conventionally made adhesive matrix type transdermal patch containing ascorbic acid and some of its derivatives including Sodium Absorbate, for the treatment of wrinkles. The patches are fabricated into crescent and other shapes with rounded corners.
In these references as well, the bioactive substances are mixed with and formulated into a pressure sensitive adhesive matrix which is subsequently coated as a single pressure sensitive adhesive layer, as described earlier.